Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.

Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibiti...

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Autores principales:	Hui-Chun Wang, Yi-Ling Tsai, Yang-Chang Wu, Fang-Rong Chang, Mei-Hsin Liu, Wen-Ying Chen, Chin-Chung Wu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f467bd1ec152430ea837bb02a787d5d2
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spelling	oai:doaj.org-article:f467bd1ec152430ea837bb02a787d5d22021-11-18T07:16:36ZWithanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.1932-620310.1371/journal.pone.0037764https://doaj.org/article/f467bd1ec152430ea837bb02a787d5d22012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22701533/?tool=EBIhttps://doaj.org/toc/1932-6203Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity.Hui-Chun WangYi-Ling TsaiYang-Chang WuFang-Rong ChangMei-Hsin LiuWen-Ying ChenChin-Chung WuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37764 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hui-Chun Wang Yi-Ling Tsai Yang-Chang Wu Fang-Rong Chang Mei-Hsin Liu Wen-Ying Chen Chin-Chung Wu Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
description	Withanolides are a large group of steroidal lactones found in Solanaceae plants that exhibit potential anticancer activities. We have previously demonstrated that a withanolide, tubocapsenolide A, induced cycle arrest and apoptosis in human breast cancer cells, which was associated with the inhibition of heat shock protein 90 (Hsp90). To investigate whether other withanolides are also capable of inhibiting Hsp90 and to analyze the structure-activity relationships, nine withanolides with different structural properties were tested in human breast cancer cells MDA-MB-231 and MCF-7 in the present study. Our data show that the 2,3-unsaturated double bond-containing withanolides inhibited Hsp90 function, as evidenced by selective depletion of Hsp90 client proteins and induction of Hsp70. The inhibitory effect of the withanolides on Hsp90 chaperone activity was further confirmed using in vivo heat shock luciferase activity recovery assays. Importantly, Hsp90 inhibition by the withanolides was correlated with their ability to induce cancer cell death. In addition, the withanolides reduced constitutive NF-κB activation by depleting IκB kinase complex (IKK) through inhibition of Hsp90. In estrogen receptor (ER)-positive MCF-7 cells, the withanolides also reduced the expression of ER, and this may be partly due to Hsp90 inhibition. Taken together, our results suggest that Hsp90 inhibition is a general feature of cytotoxic withanolides and plays an important role in their anticancer activity.
format	article
author	Hui-Chun Wang Yi-Ling Tsai Yang-Chang Wu Fang-Rong Chang Mei-Hsin Liu Wen-Ying Chen Chin-Chung Wu
author_facet	Hui-Chun Wang Yi-Ling Tsai Yang-Chang Wu Fang-Rong Chang Mei-Hsin Liu Wen-Ying Chen Chin-Chung Wu
author_sort	Hui-Chun Wang
title	Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
title_short	Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
title_full	Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
title_fullStr	Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
title_full_unstemmed	Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
title_sort	withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f467bd1ec152430ea837bb02a787d5d2
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Withanolides-induced breast cancer cell death is correlated with their ability to inhibit heat protein 90.

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